Loss of RPA1 induces Chk2 phosphorylation through a caffeine-sensitive pathway
Loss of RPA1 induces Chk2 phosphorylation through a caffeine-sensitive pathway
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DOI：
10.1016/j.febslet.2004.11.066
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发表时间：
2005-01-03
期刊：
影响因子：
3.5
通讯作者：
Wang, HG
中科院分区：
文献类型：
--
作者：
Araya, R;Hirai, I;Wang, HG
RPA是DNA复制、修复和重组的重要组成部分，但其参与细胞周期检查点的信号传导尚不清楚。在这项研究中，我们表明，敲低RPAI的siRNA双链诱导ATM（Ser1981）和Chk2（Thr68），但不Chk1（Ser345）磷酸化，并导致p21在HeLa细胞上调。然而，诱导Chk2（Thr68）磷酸化和p21表达RPA 1 siRNA转染可以完全阻断ATM抑制剂咖啡因。此外，转染靶向ATM的siRNA显著降低RPA 1敲低细胞中的Chk2（Thr68）磷酸化。综上所述，这些结果表明，RPA 1的损失激活Chk2信号转导途径在ATM依赖性的方式。(C)2004年欧洲生物化学学会联合会。Elsevier B.V.出版，保留所有权利。
RPA is an important component of DNA replication, repair and recombination, but its involvement in the signaling of cell-cycle checkpoints is not well understood. In this study, we show that knockdown of RPAI by siRNA duplexes induces ATM (Ser1981) and Chk2 (Thr68), but not Chk1 (Ser345) phosphorylation and results in p21 upregulation in HeLa cells. However, the induction of Chk2 (Thr68) phosphorylation and p21 expression by RPA1 siRNA transfection can be completely blocked by the ATM inhibitor caffeine. Moreover, transfection of siRNAs targeting ATM dramatically reduces Chk2 (Thr68) phosphorylation in RPA1 knockdown cells. Taken together, these results suggest that loss of RPA1 activates the Chk2 signaling pathway in an ATM-dependent manner. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.